Induction of tolerance of contact hypersensitivity by blocking CD28 Signal

1)B7分子在AD和CD中的表达在本研究中，我们研究了共刺激分子在AD和CD中的表达和功能，这些分子在正常对照组中未检测到。在特应性皮炎患者的非皮损皮肤中检测到CD86，但未检测到CD80。特应性皮炎CD80的表达为42%，CD86的表达全部为阳性。CD86强于CD80的结果在CD皮损中也被检测到。我们进行了抑制试验。抗CD86单抗可完全抑制DP粗提物刺激的T细胞增殖，提示CD86可能在AD和CD2的发病机制中起重要作用。2)半抗原TNBS诱导郎格汉斯细胞弱表达B7-1(CD80)和中等表达B7-2(CD86)及器官培养小鼠皮肤中这两种分子的表达。皮内注射半抗原化EC可诱导出半抗原特异性的接触敏感性，与抗B7-2(CD86)或B7-1(CD80)抗体孵育后，将半抗原处理的EC注射到小鼠体内，所产生的接触敏感性反应降至对照反应的50%以下。抗B7-2和抗B7-1mAb在体外也能抑制半抗原特异性淋巴细胞增殖或同种异体混合淋巴细胞反应，提示半抗原诱导的共刺激信号在小鼠接触敏感性的诱导中起重要作用。

1) The B7 nolecules expression in AD and CDIn the present study, we investigated the expression and function of co-stimulatory molecules in AD and CD.These molecules were not detected in normal control subjects. In non-lesional skin of atopic dermatits, CD86 but not CD80 was detected. Inlesional atopic dermatits, CD80 was expressed 42%, while CD86 was expressed in all case. Similar results of the stronger expression of CD86 over CD80 was detected in the lesional skin in CD.We conducted the inhibition test. Anti-CD86 mab completely inhibite T cell proliferation stimulated with crude extract of DP in the epidermal cell as antigen presenting cells.These data indicate that CD86 expressed on Langerhans cells may play an important part in the pathogenesis of AD and CD.2) In vitroThe hapten, TNBS,induced weak B7-1 (CD80) and moderate B7-2 (CD86) expression on Langerhans cells and mRNA expression of both molecules in organ-cultured murine skin. The intradermal injection of haptenated EC induced hapten-specific contact sensitivity.When hapten-treated EC were injected into mice after incubation with anti-B7-2 (CD86) or B7-1 (CD80) antibody the resultant contact sensitivity reaction was decreased to less than 50% of the control reaction. Anti-B7-2 and antiB7-1mAb also inhibited hapten-specific lymphocyte proliferation or the allogeneic mixed lymphocyte reaction in vitro.These data indicated that costimulatory signals induced by a hapten on Langerhans cells play an important roles in the induction of contact sensitivity in mice.